Rituximab for the Treatment of Wegener's Granulomatosis and Microscopic Polyangiitis (RAVE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.

Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

Eight centers in the United States and one center in the Netherlands (Groningen) enrolled 197 Antineutrophil cytoplasmic antibodies (ANCA)-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis between December 30, 2004 and June 30, 2008.

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

At a screening visit, participants underwent procedures to establish inclusion/exclusion criteria and then sign the informed consent form.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

The Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (WG) is a validated disease activity index. The BVAS/WG is designed to document new or worsening clinically active vasculitis and consists of a set of items divided into nine organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease. In this study, the primary end point was a BVAS/WG score of 0 and successful completion of the prednisone taper at 6 months.

VDI [1] [Units: Score units]Mean (Standard Deviation)

1.4 (1.8)

1.0 (1.4)

1.2 (1.7)

[1]

Vasculitis Damage Index. The VDI is a validated measure for damage assessment in vasculitis. The index comprises 64 items of damage (divided into 11 organ based systems) representative of damage incurred to patients with systemic vasculitis. Scores for this index range from 0 to 64, with higher scores indicating more severe damage.

Rate of Selected Adverse Events Experienced by Participants Receiving Rituximab Versus Those Receiving Conventional Therapy [ Time Frame: Through common close-out (defined as 18 months after the last participant is enrolled in the trial) ]

Time to Complete Remission (BVAS=0, Off Glucocorticoids) From the Visit 1 Baseline Visit in the Two Treatment Groups

Measure Description

Time to complete remission is defined as the number of days from baseline visit (Visit 1) to a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)[1] of 0 and completing taper of glucocorticoid by 6 months post-randomization.

[1] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease

Time Frame

18 months post-randomization

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Time to Complete Remission (BVAS=0, Off Glucocorticoids) From the Visit 1 Baseline Visit in the Two Treatment Groups [Units: Days]Number (95% Confidence Interval)

25% Quartile (95%CI)

176
(173 to 177)

177
(175 to 178)

50% Quartile (95%CI)

180
(178 to 182)

183
(180 to 187)

75% Quartile (95%CI)

189
(183 to 253)

266
(190 to 287)

Statistical Analysis 1 for Time to Complete Remission (BVAS=0, Off Glucocorticoids) From the Visit 1 Baseline Visit in the Two Treatment Groups

Groups [1]

All groups

Statistical Test Type [2]

Superiority or Other

Statistical Method [3]

Log Rank

P Value [4]

0.147

Cox Proportional Hazard [5]

1.3

95% Confidence Interval

0.9 to 1.8

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

No text entered.

[2]

Details of power calculation, definition of non-inferiority margin, and other key parameters:

No text entered.

[3]

Other relevant method information, such as adjustments or degrees of freedom:

The log-rank test assesses the difference between the two treatment arms in the pattern of achieving complete remission

[4]

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

No text entered.

[5]

Other relevant estimation information:

The hazard ratio and confidence interval are based on a Cox proportional hazard model comparing rituximab to the control group, adjusting for clinical study site, ANCA type, and glucocorticoid use prior to baseline.

8. Post-Hoc:

Number of Subjects Experiencing Serious Adverse Events [ Time Frame: Randomization to censor at Crossover, Open-label or Best Medical Judgment (up to 18 months post-randomization) ]